Cystic fibrosis (CF) is caused by a defective gene and its protein which causes the body to produce abnormally thick and sticky mucus

Basic defect is a faulty chloride transport that causes mucus build up that results in lung dysfunction, pancreatic insufficiency, intestinal diseases, and infertility

Most common life-threatening genetic disorder in Caucasians

Autosomal-recesesive disorder with more than 1900 mutations in the CFTR (CF transmembrane conductance regulator) gene

No identifiable cure is known

CFTR gene codes for a protein called the cystic fibrosis transmembrane conductance regulator

Function of CFTR protein: • Channel in membrane of cells that produces mucus,

sweat, saliva, tears, and digestive enzymes

• Transports chloride into and out of cells; helps control movement of water in tissues for thin mucus production

• Transports sodium ions across cell membranes; important for function of organs

In 1938- 70% of CF babies died within the first year of life

Average life expectancy age today is 37 years old

The most prevalent CF-causing mutation in the Caucasian population, 86% of CF alleles of cases is the F508del mutation

Mutation in the gene for the CFTR

protein. The mutation deletes three

nucleotides that code for phenylalanine.

Causes a person to produce CFTR

without phenylalanine

CFTR protein breaks down because of its

abnormality and cannot escape to move

to its correct cell location

Approximately 80,000 people in the

world are diagnosed with CF. 30,000 of

those 80,000 people are in the United

States

1 in 3500 live births have Cystic Fibrosis

More than 70% of patients are diagnosed

by age two.

More than 45% of the CF patient

population is age 18 or older

Neonatal cystic fibrosis screening

First test: A sample of blood sample is

taken from the bottom of the baby's foot

or a vein in the arm

The blood sample is examined for

increased levels of immunoreactive

trypsinogen (IRT), a protein produced by

the pancreas that is linked to CF

Gold standard for

diagnosis is the

sweat chloride test

(pilocarpine

iontophoresis)

Test used to

induce sweating

then the sweat

electrolytes are

measured

For infants up to 6 months of age • Chloride levels of:

• Less than 29 mmol/L=CF is very unlikely

• 30-59 mmol/L= CF is possible

• Greater than 60 mmol/L= CF to be diagnosed

For people older than 6 months of age • Chloride levels of:

• Less than 39 mmol/L= CF is very unlikely

• 40-59 mmol/L= CF is possible

• Greater than 60 mmol/L= CF to be diagnosed

Other Tests Prenatal Screening

• Genetic testing can show if the fetus has CF • Amniocentesis- removing small amounts of fluid from the

sac around the baby • Tested to see if the CFTR genes are normal

• Chorionic villus testing- removing a tissue sample from placenta to test for CF

Chest x ray Sinus x-ray Lung function tests Sputum culture Trypsin and chymotrypsin in stool

Back pain and headaches in 89% of

adults with CF

Chest pain in 16-64% of CF adults

Pain can cause anxiety and depression

Females are observed to have a lower

quality of life

Sleep disturbances can occur

• Patients with airflow limitation; have

sleep related hypoventilation,

hypovolemia and hypoxemia

• Mucus and gastric reflux can cause

nocturnal cough episodes

• Pain

Congenital bilateral absence of the vas deferens (CBAVD) accounts for 1-2% of male infertility

Men: All men with CF are azoospermia, infertile, and have CBAVD

50% of men with CBAVD carry two or more CFTR mutations

Women can be fertile; controversial to whether or not they should become pregnant

Cystic Fibrosis

Transmembrane

Regulator

Water follows chloride

Thick mucus develops

Salty sweat

Frequent Infections

(Pneumonia, Bronchitis)

Nasal polyps

Cough and sputum

production

Wheezing and air

trapping

Digital clubbing

Infertility

Failure to Thrive

Edema

(hypoproteinemia)

Chronic pancreatitis

Cirrhosis

Pancreatic exocrine

insufficiency

Steatorrhea

Lungs

Pancreas

Liver

Intestines

Sinuses

Sex Organs

Airway Surface Liquid

Cilia

Bacteria

Inflammation

Bronchioles in Young

Adult with CF:

The mucous is so thick that it is typically

anaerobic

Biofilms form easily in this environment

Neutrophils have poor mobility to fight

off infections

Pseudomonas aeruginosa • Present in 80% of adult patients

• Gradual decrease in lung function

• Poor clinical status

• Drug resistant (antibiotics treatment usually

ineffective)

Pathophysiology

Pathophysiology

Bicarbonate

Volume

pH

Anatomy

Lipase excretion must be below 10%

before symptoms appear

85% of CF patients require enzyme

replacement therapy due to pancreatic

insufficiency (PI)

Meconium Ileus

Maldigestion/absorption • Failure to Thrive/Growth Retardation

• Steatorrhea

• Deficiencies in fat soluble vitamins

Cystic Fibrosis Related Diabetes (CFRD)

Affects about 1/3 of adult CF patients

Due to beta cell degradation

Frequent OGTT recommended

As CF longevity increases more

microvascular complications are present

Typical diabetic diets are inappropriate

Increased energy needs through a high

fat diet, also high starch

Limited treatment is typical because of

treatment demands of CF • risk noncompliance/overwhelming patient

Insulin is used when necessary

Liver disease is the 3rd cause of death in CF

Fatty liver causes hepatomegaly

Commonly asymptomatic

Focal Biliary Fibrosis

Severe scarring can lead to cirrhosis

Varices, hemorrhaging

Best treatment: Liver transplant

Distal Intestinal Obstructive Syndrome

DIOS • Due to thickened fecal matter

• Adult equivalent of maconeum ileus

Rectal Prolapse

Preventing and controlling lung infections

Loosening and removing mucus from the lungs

Preventing and treating intestinal blockage

Providing adequate nutrition and absorption

Antibiotics

Mucus thinning drugs

Bronchodilators

Oral pancreatic enzymes

Inflammatory treatment

Postural Drainage and Percussion • 4-5 minutes in 2-3 positions, 1-4 times per day

Mechanical Percussor

Inflatable Vests: high frequency chest wall oscillation

Active Cycle of Breathing

Positive Expiratory Pressure • Masks increase force required to exhale

Long term program to improve lung function and

overall well-being Attended weekly

Includes:

• Exercise training

• Nutritional counseling

• Energy conserving techniques

• Breathing strategies

• Psychological counseling or group support or both

• Education on how to manage disease

In 2008 CAM was used by 75% of patients

Examples:

Garlic Capsules: antibacterial properties

Ginseng: antimicrobial

Curcumin: Increase CFTR activity

Only limited evidence of their effectiveness.

Exercise is always recommended

Clears the airway and improves lung

function

Helps improve quality of life

Higher levels of aerobic exercise have

been associated with prolonged survival

Aerobic training is essential to increase VO2 peak

(increase survival)

Benefits from strength training. Anaerobic training can

help increase aerobic capacity

Inspiratory muscle function (IMF) is intense breathing

exercises that strengthen the muscles around the lungs

Without IMF, pulmonary compliance decreases and

residual volume increases

Most severe conditions and other treatments are no

longer working

Must be healthy enough for a transplant (only affected

by the disease causing the demise of the lung)

CF is the third most common reason in adults

CF is the most common reason in children

Lung function tests

Blood tests

Chest CT scan

For most severe cases, when other treatments

fail

High risk procedure:

• Mortality rates:5-20%

30% suffer from post-surgical complications

Only way to restore function

5 year survival rates:

• 72% with transplants

• 33% without transplants

Single-lung transplant s not performed

Double-lung transplant

• Usually takes 6-12 hours

Living donor lobar lung transplant

• Healthy adult donates a segment, or lobe, of one lung to

another person

Lung transplants are last option

Possibility of improving quality of life

Serious Risks

• The recipients’ body may reject the lung

• Infections

Survival Rates • About 78% of patients survive the first year

• 63% of patients survive 3 years

• 51% of patients survive 5 years

Goal: control malabsorption,

maldigestion, provide adequate

nutrients, promote optimal growth or

maintain weight, support pulmonary

function, and prevent nutrient

deficiencies.

* MNT is specific to each patient;

coordinated with other treatments,

medications, and chest physical therapy.

replacing digestive enzymes

respiratory therapy

COX inhibitors to decrease inflammation

Agents that increase cAMP (like

theophylline) to open chloride channels

Monitor ongoing nutrition status

Supply pancreatic enzyme replacement

therapy (PERT)

Meet increased energy requirements

Provide vitamin/mineral supplements

PERT is first step taken to correct

maldigestion/malabsorption.

Microspheres are taken orally, designed

to withstand the acidic stomach, and

release enzymes in the duodenum for

digestion of macronutrients.

The degree of pancreatic insufficiency,

amount of food eaten, and types of

enzymes taken determine the quantity to

take.

the enzyme dosage per meal is adjusted

to control GI symptoms (steatorrhea) and

promote growth.

monitoring fecal elastase, fecal fat, or

nitrogen balance may help evaluate

adequate enzyme dosage and efficacy.

Fecal elastase is the enzyme secreted by

the pancreas to digest proteins and is

involved in hydrolysis of peptide bonds.

Evaluate and monitor growth and

development (body composition, BMI, wt,

ht, head circumference, bone status, etc)

Identify degree of pancreatic

insufficiency

Determine PERT recommendation

Energy Intake:

Based on sex, age, BMR, physical activity, respiratory

infection, severity of disease, and severity of

malabsorption

There are equations to calculate energy needs when

labs aren't available.

CF patients shouldn't decrease PA but rather increase

energy intake

For Children: high energy (based on growth needs),

moderate to high fat, and complementary PERT

For Adults: high energy (to maintain weight)

CHO needs: needs change as disease progresses

CF patients may develop lactose intolerances

Protein needs: Slightly increased, but 15--20% should meet DRI for protein

requirements

FAT needs: CF patients have increased fat needs; 35-40% of total kcals

(especially sources of EFA)

Check for EFA deficiencies in regular lipid profiles

Also watch for fat-soluble vitamin deficiencies since there is

likely fat malabsorption.

Fat intolerances found in stool samples.

Water soluble vitamins: Adequately absorbed; requirements are met by diet and

multivitamin/mineral supplement.

Fat soluble vitamins: Usually inadequately absorbed (fat malabsorption)

Low serum vitamin A - impaired mobilization and

transportation from liver.

Decreased vitamin D - related to decreased bone mineral

content

Low vitamin E - hemolytic anemia and abnormal

neurologic findings.

Vitamin K deficiency - secondary to antibiotics or liver

disease.

Intake should meet CF patients gender/age

recommendations.

Minerals to watch:

Na requirements increase because increased

losses in sweat. Deficiency is evident with

lethargy, vomiting, and dehydration.

Supplemental salt is required only in some

conditions (infants b/c low Na content in BM,

Formula and baby food, adults and children

during fever, hot weather, or exercise)

Calcium - watch for decreased bone

mineralization during childhood esp.

Iron - check yearly in children, and

monitor hgb and hct

Zinc - decreased absorption and

increased zinc in stools (esp in children

and infants). Also related to vitamin A

levels.

MEET THE NUTRIENT REQUIREMENTS

Infants: PERT by mouth or added to baby

food, supplementation of high-calorie

formula.

Children and adults: Regular and enjoyable

mealtimes, larger food portions, extra

snacks, high-nutrient density, fortified

beverages, puddings, etc. *feeding tube is alternative for patients who can't

meet nutrient needs orally.

*TPN is used short term & after GI surgery.

Results can be evidenced in improved

weight gain, slowed decline in

pulmonary function, decreased

respiratory infection, and improved

sense of well being and quality of life.

Age: 14

Female

Student

Mother is 41,

grandmother is 66,

half-brother is 5

Caucasian

"I caught a cold, and

it has just gotten

worse. My regular

treatments were

not working, and

my doctor says I

probably have

pneumonia."

Current

anthropometrics:

Ht: 5'5"

Wt: 102 #

3 months ago:

UBW: 110-115 #

Diagnosed with CF at 6 mos.

Since then uneventful disease course.

Hospitalized several times for respiratory

infections but otherwise has been maintained

by outpatient therapy.

Seen yearly in CF clinic

Uses high-frequency chest compression for 1

hour twice daily

PMH - seen in hospital over year ago.

Very active, runs 3-5 miles 5-6x week.

Meds: Pancrease (1-3 capfuls after meals), Prevacid

(20mg daily), Humabid (1/2 tablet every 12 hours),

multivitamin and Proventil PRN.

Family Hx: T2DM maternal grandmother, and CF

paternal great aunt (deceased)

Nutrition Hx: Not good appetite, Never knows how

much Pancrease to take. Likes most foods, but

never drinks milk. Likes F/V but doesn't eat many.

“I am not really home for meals that much”

“I take more pancrease if I eat more fat”

AM - rarely eats

Lunch - 3 T crunchy PB or 2 oz ham + 2 oz swiss

cheese sandwich, 2-3 oz chips, 1 orange or

other fruit, water

Dinner - 5-6 oz of chicken, pork or beef (grilled

or baked), 1-2 c raw vegetables on lettuce, 1/4

c ranch dressing, 1 c pasta, potatoes, or rice,

usually with 1-2 T margarine, water.

*really depends on whether eats at home or

friends'

Inappropriate administration of medication

related to repeated infection as

evidenced by pneumonia and cold.

Inadequate oral intake related to lack of

nutrient absorption as evidenced by

weight loss.

AM - 1 slice toast with margarine, 1 piece

of fruit, 1 c milk

Lunch - 2 slices bread, 3-4 oz ham or other

lunch meat, 2-3 oz swiss cheese, lettuce,

tomato, mayonnaise, mustard (sandwich),

1 piece of fruit, caloric drink

Dinner - 3-4 oz chicken or beef, 1 cup

pasta or rice, cream sauce, steamed

vegetables with margarine, 1 cup milk. *avoid "diet" or low fat items, and increase fat intake.

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